The long term goal of the proposed research is to define more clearly the spectrum of pharmacological activity of digitaloid substances especially as such activity is related to the toxicology of these substances. More precisely, two of the possible sites at which cardiac glycosides may act to produce sympathomimetic effects will be investigated. One possible site of action is the central nervous system (CNS). With the use of defined lesions in cats (e.g., decerebration) I will attempt to locate the general level(s) within the CNS at which digitalis acts. The mechanism by which digitalis increases sympathetic outflow will be investigated by studying the effect of digitalis on potentials which are evoked in postganglionic sympathetic nerves by electrical stimulation of discreet regions of the CNS. The sympathetic nerve ending is the other potential site where cardiac glycosides may act to increase the concentration of norepinephrine at the beta-adrenergic receptors of the heart. I will determine whether or not these drugs significantly alter the uptake and/or release of norepinephrine by cardiac sympathetic nerve endings. In addition to defining extra-myocardial sites of action of digitalis (i.e., actions that are not directly on myocardial tissue), this investigation will determine whether or not there are any differences in the spectra of pharmacological activity of different digitaloid substances (particularly with regard to sympathomimetic actions).